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新型三环苯并[4.5]环庚[1.2]吡啶衍生物作为NMDA/NR2B拮抗剂的合成与评价

Synthesis and evaluation of novel tricyclic benzo[4.5]cyclohepta[1.2]pyridine derivatives as NMDA/NR2B antagonists.

作者信息

McIntyre Charles J, McCauley John A, Bednar Bohumil, Bednar Rodney A, Butcher John W, Claremon David A, Cunningham Michael E, Freidinger Roger M, Gaul Stanley L, Homnick Carl F, Koblan Ken S, Mosser Scott D, Romano Joseph J, Liverton Nigel J

机构信息

Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.

出版信息

Bioorg Med Chem Lett. 2009 Sep 1;19(17):5132-5. doi: 10.1016/j.bmcl.2009.07.028. Epub 2009 Jul 10.

DOI:10.1016/j.bmcl.2009.07.028
PMID:19648007
Abstract

A novel series of annulated tricyclic compounds was synthesized and evaluated as NMDA/NR2B antagonists. Structure-activity development was directed towards in vitro optimization of NR2B activity and selectivity over the hERG K(+) channel. Preferred compounds were subsequently evaluated for selectivity in an alpha(1)-adrenergic receptor binding counter-screen and a cell-based assay of NR2B activity.

摘要

合成了一系列新型稠合三环化合物，并将其作为NMDA/NR2B拮抗剂进行评估。构效关系研究旨在对NR2B活性进行体外优化，并提高其对hERG钾通道的选择性。随后对优选化合物进行α(1)-肾上腺素能受体结合反筛选和基于细胞的NR2B活性测定，以评估其选择性。

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